H08: Pemphix to pemphigus vulgaris: the journey to classifying blisters

E. Butt¹ and I. Ashraf²

¹City Hospital, Birmingham, UK and ²Solihull Hospital, Solihull, UK

The words pemphix in Greek, nufākkha in Arabic, ababu’oth (bu’ah) in the Old Testament and pào in Old Chinese texts were the first words used to describe blisters. Of these, ‘pemphigus’, derived from the Greek root pemphix, is the only term that has translated into the modern medical world. François Boussier de Sauvages (1706–1767), a French physician, published the first medical classification of skin diseases, which proposed the initial definition of pemphigus. He described it as an acute, febrile, blistering disease lasting only 2 weeks, similar to our modern-day definition of erythema multiforme. However, it was Johann Ernst Wichmann (1740–1802) who later correctly defined pemphigus as a chronic, rather than acute, bullous disorder. Wichmann also accurately observed the dislodgement of the epidermis caused by shearing forces in pemphigus, later coined ‘Nikolsky sign’ by Pyotr Nikolsky (1858–1940) in his doctoral thesis of pemphigus foliaceus. However, few physicians agreed with Wichmann’s classification, and continued to use pemphigus as a broad term for blistering disorders. Similarly, Robert Willan, in his ‘Description and treatment of cutaneous diseases’ (1798) had a limited perspective of pemphigus vulgaris (PV) as a febrile, bullous eruption of short duration, and instead used the term ‘pompholyx duitinus’ to describe a chronic, bullous eruption. It was not until 1869, when Ferdinand von Hebra (1816–1880) established pemphigus as a chronic disease ‘…that runs a slow course…blebs may be present in large numbers at the same time… [whilst] fresh ones are continually breaking out at different parts…’. He separated PV into ‘malignus’ and ‘benignus’, with ‘benignus’ bearing a resemblance to modern-day bullous pemphigoid (BP). A key histological feature of PV is acantholysis, a term coined by Heinrich Auspitz (1835–1886), derived from the Greek akantha, meaning thorn, and lysis, meaning loosening. However, this was not a recognized hallmark until it was published by Darier, Civatte and colleagues in their ‘Nouvelle pratique dermatologique’ in 1936. Additionally, Walter Lever (1909–1992) recognized the absence of acantholysis in BP, in contrast to its presence in PV, establishing a clear difference between the diseases. By 1964, with the assistance of immunofluorescence techniques, Ernst Beutner and Robert Jordan discovered specific autoantibodies that cause the destruction of intercellular connections between keratinocytes, as seen in pemphigus. These were later recognized to target desmoglein (Dsg)1 and Dsg3 proteins. Finally, the condition ‘pemphigus vulgaris’ was defined as a separate autoimmune disease, rather than as a term to describe all bullous disorders.